Duvelisib

Some news in the world of pharma companies in the last week that is probably relevant for Follicular Lymphoma patients:  AbbVie, Inc. has announced a partnership with Infinity Pharmaceuticals to develop and commercialize Duvelisib, a kinase inhibitor. CNN, plus a whole lot of other news outlets, have details on the deal, and who is going to make money if things go well, which is great, but I really don't care.

What I do care about is that someone thinks they can make money off of Duvelisib, which means they'll probably put some effort into eventually making it available to us.

Duvelisib is, as I said, a kinase inhibitor. Protein kinases are enzymes that are necessary for certain functions to happen to cells. Kinase inhibitors block those enzymes from doing their job, and thus they keep cells from doing things they aren't supposed to do.

Duvelisib is, specifically, a PI3K inhibitor, which means it blocks an enzyme that is necessary for a cancer cell to grow and survive. There are actually several different types of PI3K inhibitors, and they block different parts of the enzyme. And there are a bunch of different PI3K inhibitors already developed or in development, including Idelalisib, so we have a pretty good idea that this type of treatment, in general, will work. (In fact, maybe it is the recent excitement about Idelalisib that pushed these companies to make a deal?)

So far, Duvelisib has been studied in a couple of phase 1 clinical trials, and one phase 2 trial involving refractory indolent NHL patients (which, I assume, includes some Follicular Lymphoma patients). Lymphoma Hub has some basic information about Duvelisib, including information about these clinical trials, as does Lymphomation.org, under its alternate name IPI-145.

Wall Street is excited. That seems like a good reason to keep an eye on this one.

Blue Ribbon Time

It's that time of year -- country fair time. Time to test my skills in the garden and the kitchen against my peers. (And my daughter.)

Long-time readers know that I have won blue ribbons for my tomatoes for the last two years. And that I am in competition with my daughter for the most blue ribbons (last year, she won for best cupcakes, best decorated cake, and best clay sculpture).

Let me begin with this -- it was not a good summer for vegetables. (You can probably guess, from that sentence, how well I did at the fair in the vegetable categories.) This was an unusually cool summer (until a few weeks ago), so my warm-weather veggies like peppers and eggplants never really got going. And when I went away for two weeks in July, all of my veggies had growth spurts, which either split some of their vines (tomatoes) or exhausted their fruit (cucumbers). Plus, we've had a groundhog problem, and this critter loves zucchini leaves and flowers. It was just not a good year.

All I had to enter in the fair was a few tomatoes. Without dwelling on it, I ended up with two third-place ribbons, for my Big Boy tomatoes and my green cherry tomatoes. There will be no three-peat this year for Lympho Farmer Bob.

Lympho Baker Bob, on the other hand, did OK for himself. While I expected some love for my Boston Cream Cupcakes (truly awesome) and Chocodoodle Snickerdoodle cookies (pretty darn good), and got none, I did win blue ribbons for my Chocolate Chip Banana muffins and my Ginger Carrot Bran muffins. So now I am officially both an award-winning baker and an award-winning gardener. My children aren't happy about my strutting around like a proud rooster.



My daughter, on the other hand, won a blue ribbon for her frosted chocolate cake, and some second-place ribbons for her sculptures and cupcakes. She will be the first to admit that she didn't put as much effort into things this year as in the past. And I though my two blues meant that she and I were now tied....but no. She won another blue ribbon for her homemade earrings. So she's ahead of me in the overall blue ribbon tally.

Which is great. As I've written before, I think this kind of competition is good for her. It's fun, with little pressure, and it gives her a chance to work hard at something and see the results pay off.

And just as importantly, it gives me a chance to do the same thing. I know lots of people have "bucket lists," with things they want to do before they die, and sometimes a cancer diagnosis really makes that list more important. But I've never been a bucket list guy. I don't want to someday look at my list and regret that I didn't get to do X or Y. Too much pressure to check something off.

I'd much rather enjoy the experiences as they come. Going to Scotland and England and seeing my kids enjoy themselves so much was a joy for me. I'd love to go back, and see and do the things that we didn't get a chance to see and do this time. If I don't get to do that, no regrets.

Same with the blue ribbons. If I'd come away this year with nothing, then no big deal. Getting up at 4:00am to bake muffins before I got the kids to school, and turning them in by 8:30am -- that was the fun experience. The ribbons are just the icing on the cake (pun intended).

I don't ever have a day where I don't remember that I have cancer. But that doesn't mean I have to stop myself from taking the opportunities that come to me.

Lifestyle Risks for Follicular Lymphoma

The Journal of the National Cancer Institute's Monographs has published a massive and fascinating study of risk factors in 11 types of Non-Hodgkin's Lymphoma, including Follicular Lymphoma. They come to some interesting conclusions, and they come with an important warning.

But first, the massive study itself: The International Lymphoma Epidemiology Consortium looked at 20 case-controlled studies of NHL (that is, studies that compared people with NHL to people without it), looking at a total of over 17,000 NHL patients and over 23,000 non-NHLers. They did some statistical wizardry to make sure everything was comparable, and then broke it all up into the 11 types of NHL to see what they could find. The studies came from a big chunk of the world -- North America, Europe, and Australia -- and they looked to see if there was any connection between getting an NHL subtype and factors such as medical history, family history, lifestyle, and occupation.

Of course, around here we're most interested in the Follicular Lymphoma study, aren't we?

For this study, they looked at 3,530 FL patients, comparing them with over 20,000 non-NHLers in the control group. Follicular Lymphoma has always been one of those funny cancers that hasn't had a lot of risk factors associated with it. Up until now, there seems to have been a connection between smoking and contracting Follicular Lymphoma, but most other factors have been big maybes. Maybe it's higher if you worked on a farm. Maybe it's higher if you were around certain chemicals. Maybe it's higher if you had serious infections. But nothing really definite.

This study did find some more definite connections. Comparing Follicular Lymphoma patients to non-NHL patients, they found that the risk of contracting Follicular Lymphoma is higher if you

• have a first-degree relative with NHL 
• had a high body mass index as a young adult
• worked as a spray painter
• are a woman with Sjögren syndrome (an autoimmune disease)

On the other hand, risk is lower if you

• have asthma, hay fever, and food allergy 
• have received  blood transfusions 
• have high recreational sun exposure 
• have worked as a baker or miller
• are a university/higher education teacher 

Now, to me, those are some really specific risk factors. (Do you know how many spray painters there are in the U.S. right now? Me neither, but it can't be many.)

So here are the important things to take away from this:

First, a risk factor does not automatically result in a health outcome. We've all known people who have smoked their whole lives who never developed lung cancer (or Follicular Lymphoma, for that matter). A risk factor shows an increased possibility of something, but not a definite outcome. From these lists, I have two of the factors that result in higher risk, and  two that result in lower risk. The two from the lower-risk helped me about as much as my non-cancer-sniffing dog has helped me. And there's no guarantee that the higher-risk factors resulted in my diagnosis.

Second, and maybe more importantly: I think we all have a tendency to want to know why we got this disease, especially because there's no obvious connection between risk factors and diagnosis. We can't say "Oh, I got it because I ate too many avocados as a kid. Everyone knows avocado eating leads to Follicular Lymphoma." There's nothing obvious that leads us to that conclusion.

And I think it's bad to try to make that connection. While it might satisfy our curiosity, I don't think it helps in any other ways. We have Follicular Lymphoma, and we're doing our best to educate ourselves about it and deal with it. Why dwell on the past? Does it help to say, "Oh, I never should have taken that job as a spray painter!" or "If only I'd taken that job as a baker, and spent my days off getting some recreational sun exposure!" That's done. That won't change the fact that we are Follicular Lymphoma patients right now. If knowing about risk factors just results in guilt, we're better off not knowing. We have enough negative emotions to deal with as it is.

So what's the point of a study like this?

Well, according to the researchers, it's not about individuals, and it's not about regretting the past. It's all about the future. If we can understand the kinds of risk factors that lead to different types of NHL, then maybe we can start to find clues about what causes it. There won't be a direct line between cause and effect -- cancer is never that easy. But maybe researchers can start asking some new questions about who gets NHL and who doesn't, and why. And maybe those broad questions lead to narrower ones, and they can start investigating things on a genetic level and figuring out why spray painting and BMI turns on some switches in our cells.

So, in some ways, this study doesn't matter. In others, it may matter a lot, some day.

For now, though, close this blog and leave the guilt behind.

Happy Lymphoma Awareness Month!

It's September, at that means it's time again for Lymphoma Awareness Month! Woo hoo!

I always find it a bit ironic -- as if lymphoma patients, their caregivers and loved ones needed to be reminded about lymphoma.

Really, this month is about making others aware -- people who might have it and don't know it (though we sure hope that isn't the case for anyone), people who misunderstand what it's all about, even people who have the power to do something to help us (funders, donors, legislators, voters). It's good for people to know what lymphoma is, and WHY they should know it.

To that end, some excellent organizations have put some things together to help us make others aware.

Patients Against Lymphoma, the good folks behind Lymphomation.org, have posted an updated brochure that provides some basic information about lymphoma  -- types, symptoms, treatments, etc. It can printed on both sides and distributed to anyone you think might benefit from the information.

The Lymphoma Research Foundation is again conducting their "Light it Red" campaign, encouraging people to light up buildings and landmarks in red lights to raise awareness of lymphoma (and other blood cancers) and give hope to lymphoma patients. They've got a nice list of buildings and landmarks that will be lit up, including Niagara Falls in New York and Canada, the National Concert hall in Dublin, Ireland, and the TD Garden in Boston, among others. 

And of course, the Lymphoma Coalition, made up of Lymphoma research and support organizations from around the world, publishes their annual "Know Your Nodes" quiz.  (I got 8 out of 10. Feel free to try to beat me.)

Does "awareness" really matter? Does it make any difference?

Yeah. I think it does. More people being aware of lymphoma means that more people will take it seriously if they think they might have it. (And if you do think so, get the heck off your computer and go to a doctor. Don't trust anything online that says you might or might not have it. Get a medical professional to tell you for sure.)

And, more importantly, in the last month, a whole lot more people became aware of ALS, thanks to the ALS Ice Bucket Challenge that has been spreading all over the internet. (And yes, Lympho Bob did participate.) It not only raised awareness, but also raised millions of dollars for research on the disease. Pretty darn nice.

So take some time to celebrate this month -- our month. Cancer isn't really something to celebrate, but being alive sure is.

Curcumin and Cancer

Interesting article on Curcumin and cancer fro MedicalXpress. It's not about lymphoma, but it got me thinking.

The article is called "Curcumin Blocks the Metastasis of Colon Cancer by a Novel Mechanism." Curcumin is an ingredient in the spice Turmeric, which is often used in Indian cuisine because of its flavor and bright yellow color. (And it makes an acceptable substitute for saffron in Risotto Milanese, but don't tell anyone in my family I said that.) It has long been thought that Curcumin has an effect on cancer, perhaps in blocking metastasis and spreading of colon cancer. (I say "thought to" and "possibly" because I can't find anything that doesn't use that kind of fuzzy language.) No one is rejecting the idea that Curcumin might be helpful, but it isn't being used as a common treatment for cancer, either. It isn't absorbed easily by the body, and that's one of the problems.

The study described in this article might move us away from the fuzzy language. Some researchers have found the mechanism that makes Curcumin block metastasis. It activates an enzyme that blocks a protein called cortactin in colon cancer. Cortactin is necessary for cells to move. Therefore, blocking it will keep cells (including cancer cells) from moving from one part of the body to another. It won't necessarily kill the cancer cells, but it will keep them in one place. That's a big issue for certain cancers.

Reading this reminded me of a lot the advice I got when I was first diagnosed. Someone did recommend I eat a lot of turmeric. Someone else suggested I buy some kind of juice that would cost about $15 a day. Someone else sent me a link to a special trampoline that would keep my lymphatic fluid moving and not turn to sludge (which was, they said, probably what caused my lymphoma). Someone else said I should cut out sugar.

They were all well-meaning, and I never got mad at anyone for offering me advice. They were all very sincere -- every one of them had "read it somewhere."

But, despite seeing something online or in print, none of it was ever subjected to any kind of rigorous study to see if it actually worked. Some of them might have been studied "in vitro," in a laboratory, but not "in vivo," in an actual patient. That matters. As we see more and more, it's not just the cancer cells that matter, but all of the stuff happening around the cells, all of the processes that occur to keep a cancer alive, that matter. So dropping some South American juice on a cancer cell in a petri dish and watching it die really doesn't tell you much about how that juice -- after it has been consumed and processed by the body and then sent to the cell -- will behave.

So even though that Curcumin study is important for colon cancer patients, I think it's important for us Follicular Lymphoma patients, too, but for a different reason. We all want quick fixes -- we all want a juice to drink or a food to avoid to help us. But cancer isn't that easy to deal with, as much as we'd like there to be. And Follicular Lymphoma is even harder than other cancers, given its nature. We might decide that eating Massaman Curry every day for lunch is what has made our lymph nodes shrink, when really, it has been the waxing-and-waning that sometimes occurs no matter what we do. There's no real way to tell, without the kind of rigorous study that comes from a formal clinical trial.

(And I would absolutely volunteer for a clinical trial that involved eating Massaman Curry every day, especially if it was also testing whether Pad Thai helped with Curcumin absorption.)

I'm all for doing things that help us feel good, whether it's eating curry or jumping on a trampoline. But when it comes to really attacking our lymphoma, I think science has to win out.

And if there's one important thing that I got from this article, it is this:

When my wife and I go out for our weekly lunch together, it's going to be at our favorite Indian restaurant. Because now I am have a really bad craving for some curry.

Rituxan Maintenance for Follicular Lymphoma

The newest issue of the Journal of Clinical Oncology has a report from the RESORT trial (the name stands for Rituximab Extended Schedule or Re-Treatment. Basically, the trial wanted to see which was more effective: Rituxan Maintenance (their "Extended Schedule") or just waiting until treatment is needed again, and then giving more Rituxan ("Re-Treatment").

In a nutshell, they believe that Re-Treatment when needed is the choice over Rituxan Maintenance for Follicular Lymphoma patients with low tumor burden.

Let me repeat the important part of that: with low tumor burden. The trial focused on patients with this characteristic, and the article is clear about what this means. Basically, low tumor burden has to do with size (less than 7 cm), location (not pressing on any organs), and grade (no B symptoms). What they say about Rituxan Maintenance doesn't apply to patients with more aggressive forms of Follicular Lymphoma. That's important to remember.

It's also important to remember that the RESORT trial is focused on patients whose initial treatment was straight Rituxan. It doesn't necessarily tell us anything about patients who had Rituxan Maintenance after chemo.

So this is fairly limited bunch of folks we're dealing with here.

As for the specifics of the trial: 289 FL patients were given four doses of Rituxan as a first treatment. They were then split randomly into two groups. The first group received Rituxan Maintenance -- one dose every three months. The other group was only given Rituxan when it was necessary, that is, when their lymphoma progressed enough to need it. For both groups, this went on until the Rituxan stopped working ("treatment failure").

For the patients receiving Maintenance, the median time to treatment failure was 4.3 years. For those in the Re-Treatment group, it was 3.9 years. Statistically, there really isn't any difference between them. But over that time, the Maintenance group received a median of 18 doses of Rituxan, while the Re-Treatment group received just 4.

That seems to be the kicker for the researchers -- a few extra months before treatment failure requires an additional 14 doses of Rituxan. And with those doses comes the costs in time and money and whatever emotional costs come with going for treatment. So their conclusion is: for Follicular Lymphoma patients with low tumor burden who received Rituxan as an initial treatment, Rituxan Maintenance really isn't worth it.

Interestingly, the researchers point out that they would love to see a similar trial involving patients whose initial treatment was chemo + Rituxan, comparing those who get Maintenance with those who are Re-Treated with Rituxan as needed. Maintenance is a common practice, but maybe there's reason to ask whether or not there's a better way?

The JCO article was accompanied by an editorial called "End of Rituxan Maintenance for Low Tumor Burden Follicular Lymphoma." It's a title that pretty much sums up the author's position -- he thinks the RESORT trial results tell us everything we need to know. The author doesn't only refer to the RESORT article, but also to an article from March in The Lancet that showed that Rituxan Maintenance in a similar group of patients (low tumor burden Follicular Lymphoma) resulted in a better chance of holding off the lymphoma from returning, compared to those who watched and waited. HOWEVER, the Overall Survival of the two groups was virtually the same, and there was no difference between the two groups in terms of transformation. So while the article from The Lancet might seem like a win for Rituxan Maintenance (and that's certainly the way I wrote about it, as you can see from the link), looking at different outcomes might paint a different picture of that data.

(And, to be fair, The Lancet article and the RESORT article compared two different groups. One said Maintenance was better than watching and waiting, while the other said it was not as good as treating as needed.)

My conclusion?

As with many things related to Follicular Lymphoma, we still have no real, solid evidence that one strategy is definitely better than another. Despite the confidence of that title, I don't think we've seen the "End of Rituxan Maintenance" for FL patients with low tumor burden. It might provide a push for a patient or oncologist who is sitting on the fence, but I'm sure there are plenty of folks who will continue the practice. The RESORT results didn't say Maintenance was bad or harmful, only that there might be a better way.

I can remember talking to Dr. R about Maintenance after my six rounds of Rituxan. He talked me out of it, saying there was better evidence that Maintenance worked after chemo than after straight Rituxan, and that his philosophy was to treat when necessary (very much in line with the Re-Treatment approach from RESORT). Dr. R certainly seems wise, four and a half years later, when I still haven't needed Re-Treatment of any kind.

Of course, one patient does not make a trial, so my isolated experience doesn't mean much. The lesson, instead, from my experience is that an open, two-way conversation with your oncologust is necessary when it comes time for treatment.

Visit to the Oncologist

I had an oncologist appointment this morning. Everything looks fine.

To be honest, this appointment snuck up on me -- I forgot to put it on the calendar, and I only remembered because it they gave me a reminder call yesterday. This was about 3 months since my last visit; I think I made it a month shorter than usual because I knew once school started up for everybody that things would get their usual crazy, so I'd do it before then.

I think that's a good thing that I had forgotten about it. Forgetting = not worrying = not having any problems to worry about. It was kind of the theme for this visit.

For whatever reason, Dr. R didn't have me do blood work first, like he usually does. Maybe I came in late? I still get confused about my appointment time. Because the practice is now officially a branch of the cancer hospital, I have two separate appointments -- one for a blood draw and one for the onc visit. So when they say the appointment is at 11:15, I don't know if that's for the onc or the blood. So maybe I was supposed to be there for blood work at 11:00, so he took me in at 11:15 so I would stay on schedule for him? I don't know. Still not crazy about this new set up.

Anyway, the physical exam was fine. He didn't find anything popping up that shouldn't be popping up anywhere. And then he gave me his serious face and said, "I know we've been kind of going back and forth about this, but we should probably think about a scan soon...."

"Wait," I interrupted. "I had a scan in June."

"Really?"

My wife backed me up on this.

He looked at my online records and saw that I had indeed gotten a scan in June. We talked about the results, even though we had talked about them back then. He was pleased with the results, as he should have been. And then I gave him crap for the rest of the visit.

"Jeez, doctor. I've been coming here for six and half years. I thought I was more memorable than that."

He smiled. "I think it's better for you to not be memorable."

And he's right. If I was a patient who was in the middle of treatment, or if I was a particularly tough Follicular Lymphoma case that kept recurring, or if the scan was really troubling, then maybe I would have been on his mind. But I'm just a slow-growing, waxing-and-waning, see-you-every-four-months-for-a-few-minutes kind of patient. And I can't complain about that. I'll take forgettable if those are my choices.

Plus, it's just so much fun to give him a hard time about something.

It turned out that, because I went to a new place for the scan, he was looking in the wrong place in my file for the information. An honest enough mistake, I guess.

He ordered blood work after that, and gave me a thumbs-up 5 minutes later when everything there appeared normal.

So overall, it was a good visit. An unexpected one, but a good one. I go back in late December -- I hope to have no health news for you until then.